Betaine-modified hydroxyethyl cellulose (HEC): A biodegradable mucoadhesive polysaccharide exhibiting quaternary ammonium substructures

Efiana, Nuri Ari; Kali, Gergely; Fürst, Andrea; Dizdarević, Aida; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ejps.2022.106313

Cited by 7 publications

(9 citation statements)

References 47 publications

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“…Briefly, 1 g of lipase was added to 10 mL of digestive medium, followed by centrifugation at 13400 rpm at 4 °C for 20 min. Subsequently, the supernatant was stored at 4 °C for further use . For degradation studies, 60 mg of cellulose–mercaptosuccinate was dissolved in 3 mL of digestion medium with a pH of 7.0, having been adjusted with 0.1 M NaOH before adding 3 mL of lipase solution.…”

Section: Methodsmentioning

confidence: 99%

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Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Kali,

Özkahraman,

Laffleur

et al. 2023

Biomacromolecules

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This study aims to design an anionic, thiolated cellulose derivative and to evaluate its mucoadhesive and permeation-enhancing properties utilizing enoxaparin as a model drug. 2-Mercaptosuccinic acid-modified cellulose (cellulose− mercaptosuccinate) was synthesized by the reaction of cellulose with S-acetylmercaptosuccinic anhydride. The chemical structure of the target compound was confirmed by FTIR and 1 H NMR spectroscopy. The thiol content was determined by Ellman's test. The conjugate exhibited 215.5 ± 25 μmol/g of thiol groups and 84 ± 16 μmol/g of disulfide bonds. Because of thiolation, mucoadhesion on porcine intestinal mucosa was 9.6-fold enhanced. The apparent permeability (P app ) of the model dye Lucifer yellow was up to 2.2-fold improved by 0.5% cellulose−mercaptosuccinate on a Caco-2 cell monolayer. Enoxaparin permeation through rat intestinal mucosa increased 2.4-fold in the presence of 0.5% cellulose−mercaptosuccinate compared with the drug in buffer only. In vivo studies in rats showed an oral bioavailability of 8.98% using cellulose−mercaptosuccinate, which was 12.5fold higher than that of the aqueous solution of the drug. Results of this study show that the modification of cellulose with 2mercaptosuccinic acid provides mucoadhesive and permeation-enhancing properties, making this thiolated polymer an attractive excipient for oral drug delivery.

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Section: Methodsmentioning

confidence: 99%

“…Incubation was continued for up to 24 h to determine the MSA content in the sample. The amount of NaOH required was equal to the release of MSA . Native cellulose served as a negative control.…”

Section: Methodsmentioning

confidence: 99%

Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Kali,

Özkahraman,

Laffleur

et al. 2023

Biomacromolecules

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“…However, their mucoadhesive properties can be improved by covalent attaching of various ligands providing additional bonds to the mucus layer. The synthesis of betaine-modified HEC by adding N-chlorobetainyl chloride as a reagent and pyridine as a catalyst resulted in an increase in mucoadhesive properties [ 102 ].…”

Section: Polymers As Functional Excipients For Improvement Of Ocular ...mentioning

confidence: 99%

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Račić

Krajišnik

2023

Pharmaceutics

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Dry eye syndrome and allergic conjunctivitis are the most common inflammatory disorders of the eye surface. Although eye drops are the most usual prescribed dosage form, they are characterized by low ocular availability due to numerous barrier mechanisms of the eye. The use of biopolymers in liquid ophthalmic preparations has numerous advantages, such as increasing the viscosity of the tear film, exhibiting bioadhesive properties, and resisting the drainage system, leading to prolonged retention of the preparation at the site of application, and improvement of the therapeutic effect. Some mucoadhesive polymers are multifunctional excipients, so they act by different mechanisms on increasing the permeability of the cornea. Additionally, many hydrophilic biopolymers can also represent the active substances in artificial tear preparations, due to their lubrication and moisturizing effect. With the modification of conventional ophthalmic preparations, there is a need for development of new methods for their characterization. Numerous methods for the assessment of mucoadhesiveness have been suggested by the literature. This review gives an overview related to the development of mucoadhesive liquid ophthalmic formulations for the treatment of dry eye and allergic conditions.

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“…Stability might also be the reason that glycine betaine esters, unlike phosphocholine esters, have not been described as components of cell membrane lipids. 13 Starch esters with betaine were prepared, 14 whereas cellulose 15,16 betaine esters were used as flocculants, and hydroxyethyl cellulose 17 betaine esters served as mucoadhesives. These products were prepared by a two-step reaction with thionyl chloride.…”

Section: Introductionmentioning

confidence: 99%

“…Starch esters with betaine were prepared, whereas cellulose , betaine esters were used as flocculants, and hydroxyethyl cellulose betaine esters served as mucoadhesives. These products were prepared by a two-step reaction with thionyl chloride.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and Antibacterial Efficacy of Betaine- and Choline-Substituted Polymers

Jurko

Makuc

Štern

et al. 2023

ACS Appl. Polym. Mater.

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Cationic charge has been widely used to increase polymer adsorption and flocculation of dispersions or to provide antimicrobial activity. In this work, cationization of hydroxyethyl cellulose (HEC) and polyvinyl alcohol (PVA) was achieved by covalently coupling betaine hydrochloride and choline chloride to the polymer backbones through carbonyl diimidazole (CDI) activation. Two approaches for activation were investigated. CDI in excess was used to activate the polymers’ hydroxyls followed by carbonate formation with choline chloride, or CDI was used to activate betaine hydrochloride, followed by ester formation with the polymers’ hydroxyls. The first approach led to a more significant cross-linking of PVA, but not of HEC, and the second approach successfully formed ester bonds. Cationic, nitrogen-bearing materials with varying degrees of substitution were obtained in moderate to high yields. These materials were analyzed by Fourier transform infrared spectroscopy, nuclear magnetic resonance, polyelectrolyte titration, and kaolin flocculation. Their dose-dependent effect on the growth of Staphylococcus aureus and Pseudomonas aeruginosa, and L929 mouse fibroblasts, was investigated. Significant differences were found between the choline- and betaine-containing polymers, and especially, the choline carbonate esters of HEC strongly inhibited the growth of S. aureus in vitro but were also cytotoxic to fibroblasts. Fibroblast cytotoxicity was also observed for betaine esters of PVA but not for those of HEC. The materials could potentially be used as antimicrobial agents for instance by coating surfaces, but more investigations into the interaction between cells and polysaccharides are necessary to clarify why and how bacterial and human cells are inhibited or killed by these derivatives, especially those containing choline.

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Betaine-modified hydroxyethyl cellulose (HEC): A biodegradable mucoadhesive polysaccharide exhibiting quaternary ammonium substructures

Cited by 7 publications

References 47 publications

Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Cytotoxicity and Antibacterial Efficacy of Betaine- and Choline-Substituted Polymers

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